title: Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling.
abstract: Wnt/β-catenin signalling is central to development and its regulation is essential in preventing cancer. Using phosphorylation of Dishevelled as readout of pathway activation, we identified Drosophila Wnk kinase as a new regulator of canonical Wnt/β-catenin signalling. WNK kinases are known for regulating ion co-transporters associated with hypertension disorders. We demonstrate that wnk loss-of-function phenotypes resemble canonical Wnt pathway mutants, while Wnk overexpression causes gain-of-function canonical Wnt-signalling phenotypes. Importantly, knockdown of human WNK1 and WNK2 also results in decreased Wnt signalling in mammalian cell culture, suggesting that Wnk kinases have a conserved function in ensuring peak levels of canonical Wnt signalling.
authors.affiliation: Department of Developmental and Regenerative Biology, New York, New York 10029, USA.
authors.forename: Ekatherina
authors.initials: E
authors.lastname: Serysheva
authors.forename: Hebist
authors.initials: H
authors.lastname: Berhane
authors.forename: Luca
authors.initials: L
authors.lastname: Grumolato
authors.forename: Kubilay
authors.initials: K
authors.lastname: Demir
authors.forename: Sophie
authors.initials: S
authors.lastname: Balmer
authors.forename: Maxime
authors.initials: M
authors.lastname: Bodak
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
authors.forename: Stuart
authors.initials: S
authors.lastname: Aaronson
authors.forename: Marek
authors.initials: M
authors.lastname: Mlodzik
authors.forename: Andreas
authors.initials: A
authors.lastname: Jenny
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000076204:WNK Lysine-Deficient Protein Kinase 1; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D051176:beta Catenin; C000606588:dsh protein, Drosophila; C523482:WNK2 protein, human; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human